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The metabolic consequences of evoked spreading depolarization in brain slices.

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Τίτλος: The metabolic consequences of evoked spreading depolarization in brain slices.
Συγγραφείς: Grech O; Metabolism and Systems Science, School of Medical Sciences, College of Medicine and Health, University of Birmingham, Birmingham, B15 2TT, UK., Mugo C; Metabolism and Systems Science, School of Medical Sciences, College of Medicine and Health, University of Birmingham, Birmingham, B15 2TT, UK.; Biomedical Sciences, School of Infection, Inflammation and Immunology, College of Medicine and Health, University of Birmingham, Birmingham, B15 2TT, UK., Hill LJ; Biomedical Sciences, School of Infection, Inflammation and Immunology, College of Medicine and Health, University of Birmingham, Birmingham, B15 2TT, UK., Heaselgrave SR; Center of Hypothalamic Research, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, 75390- 9077, USA., Alimajstorovic Z; Metabolism and Systems Science, School of Medical Sciences, College of Medicine and Health, University of Birmingham, Birmingham, B15 2TT, UK., Yiangou A; Metabolism and Systems Science, School of Medical Sciences, College of Medicine and Health, University of Birmingham, Birmingham, B15 2TT, UK.; Department of Neurology, University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital, Birmingham, B15 2WB, UK., Lyons HS; Metabolism and Systems Science, School of Medical Sciences, College of Medicine and Health, University of Birmingham, Birmingham, B15 2TT, UK., Mitchell J; Metabolism and Systems Science, School of Medical Sciences, College of Medicine and Health, University of Birmingham, Birmingham, B15 2TT, UK., Lavery GG; Centre for Systems Health and Integrated Metabolic Research, Department of Biosciences, School of Science and Technology, Nottingham Trent University, Clifton Campus, Nottingham, NG11 8NS, UK., Fulton D; Department of Inflammation and Ageing, School of Infection, Inflammation and Immunology, College of Medicine and Health, University of Birmingham, Birmingham, B15 2TT, UK.; Birmingham Centre for Neurogenetics, University of Birmingham, Birmingham, B15 2TT, UK., Sinclair AJ; Metabolism and Systems Science, School of Medical Sciences, College of Medicine and Health, University of Birmingham, Birmingham, B15 2TT, UK. a.b.sinclair@bham.ac.uk.
Πηγή: Scientific reports [Sci Rep] 2026 Feb 11; Vol. 16 (1). Date of Electronic Publication: 2026 Feb 11.
Τύπος έκδοσης: Journal Article
Γλώσσα: English
Στοιχεία περιοδικού: Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE
Imprint Name(s): Original Publication: London : Nature Publishing Group, copyright 2011-
Ιατρικοί όροι (MeSH): Cortical Spreading Depression*/physiology , Brain*/metabolism, Glucose/metabolism ; Glucose/deficiency ; Mitochondria/metabolism ; Ubiquinone/analogs & derivatives ; Ubiquinone/pharmacology ; Ubiquinone/metabolism ; Neurons/metabolism ; Carbon/metabolism ; Animals ; Glycolysis ; Male ; Calcium Signaling ; Energy Metabolism
Περίληψη: Spreading depolarization is a wave of neuronal and glial depolarization that propagates through brain tissue, triggering neuropeptide release and altered blood flow. It has been observed in ischemic stroke, traumatic brain injury, subarachnoid haemorrhage, epilepsy, and migraine aura. Spreading depolarization imposes a high energetic demand, and recovery impaired under metabolic substrate deficiency. Despite its clinical relevance, metabolic responses remain poorly understood, limiting therapeutic progress. We investigated metabolic effects of spreading depolarisation using an ex vivo brain slice model, aiming to characterise changes in intracellular calcium signalling, mitochondrial function, and central carbon metabolism, and to assess the impact of glucose deprivation. We further tested whether coenzyme Q10 could improve recovery under metabolically compromised conditions. Spreading depolarization increased mitochondrial activity and shifted metabolism toward anaerobic respiration and glycolysis. Glucose deprivation impaired recovery, inducing mitochondrial dysfunction and accumulation intermediates indicative of tricarboxylic acid cycle stalling and disrupted central carbon metabolism. Supplementing glucose-deprived brain slices with coenzyme Q10 shortened spreading depolarization repolarization duration, indicating enhanced metabolic recovery. These findings demonstrate that spreading depolarization imposes a significant metabolic burden, particularly under glucose limitation, and that mitochondrial-targeted interventions such as coenzyme Q10 may enhance tissue resilience in neurological disorders.
Competing Interests: Declarations. Competing interests: OG reports scientific consultancy fees from Invex Therapeutics, outside the scope of this work. AJS reports has consulted for Novartis, AbbVie, Vertex and Orion Pharma and speaker fees from Teva Uk and Novartis. She was previously a Director and Chief Scientific Officer (CSO) with shares at Invex Therapeutics.
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Grant Information: Award for Biomedical Research Sir Jules Thorn Charitable Trust; Fellowship Association of British Neurologists and Guarantors of the Brain
Contributed Indexing: Keywords: Central carbon metabolism; Coenzyme Q10; Glucose deprivation; Mitochondrial function; Multi electrode array; Spreading depolarization
Substance Nomenclature: IY9XDZ35W2 (Glucose)
1339-63-5 (Ubiquinone)
EJ27X76M46 (coenzyme Q10)
7440-44-0 (Carbon)
Entry Date(s): Date Created: 20260211 Date Completed: 20260627 Latest Revision: 20260813
Update Code: 20260813
PubMed Central ID: PMC12972070
DOI: 10.1038/s41598-026-37175-w
PMID: 41673123
Βάση Δεδομένων: MEDLINE
Περιγραφή
ISSN:2045-2322
DOI:10.1038/s41598-026-37175-w